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Molecular and Cellular Biology

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https://www.readbyqxmd.com/read/28533221/cd9-regulates-mhc-ii-trafficking-in-monocyte-derived-dendritic-cells
#1
Vera Rocha-Perugini, Gloria Martínez Del Hoyo, José Maria González-Granado, Marta Ramírez-Huesca, Virginia Zorita, Eric Rubinstein, Claude Boucheix, Francisco Sánchez-Madrid
Antigen presentation by dendritic cells (DCs) stimulates naïve CD4(+) T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II molecules (MHC-II) accumulate at MHC-II-enriched endosomal compartments, and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28533220/triptolide-assisted-phosphorylation-of-p53-suppresses-inflammation-induced-nf-%C3%AE%C2%BAb-survival-pathways-in-cancer-cells
#2
Li Zheng, Jia Jia, Huifang Dai, Lei Wan, Jian Liu, Lin Hu, Mian Zhou, Michael Qiu, Xufeng Chen, Lufen Chang, Jae Y Kim, Karen Reckamp, Dan J Raz, Zongping Xia, Binghui Shen
Chronic inflammation plays important roles in cancer initiation and progression. Resolving chronic inflammation or blocking inflammatory signal transduction may prevent cancer development. Here, we report that the combined low-dose use of two anti-inflammatory drugs, aspirin and triptolide, reduces spontaneous lung cancer incidence from 70% to 10% in a mouse model. Subsequent studies reveal that such treatment has little effect in resolving chronic inflammatory conditions in the lung, but it significantly blocks NF-κB-mediated expression of proliferation and survival genes in cancer cells...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28533219/obesity-linked-phosphorylation-of-sirt1-by-ck2-inhibits-its-nuclear-localization-and-promotes-fatty-liver
#3
Sung E Choi, Sanghoon Kwon, Sunmi Seok, Zhen Xiao, Kwan-Woo Lee, Yup Kang, Xiaoling Li, Kosaku Shinoda, Shingo Kajimura, Byron Kemper, Jongsook Kim Kemper
Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including non-alcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase-2 (CK2), the levels of which were dramatically elevated in obesity...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28507037/systemic-activation-of-nrf2-alleviates-lethal-autoimmune-inflammation-in-scurfy-mice
#4
Takuma Suzuki, Shohei Murakami, Shyam S Biswal, Shimon Sakaguchi, Hideo Harigae, Masayuki Yamamoto, Hozumi Motohashi
The transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2) plays crucial roles in the defense mechanisms against oxidative stress and mediates anti-inflammatory actions in various pathological conditions. Recent studies have shown that the dysfunction of regulatory T cells (Tregs) is directly linked to the initiation and progression of various autoimmune diseases. To determine the Treg-independent impact of NRF2 activation on autoimmune inflammation, we examined Scurfy (Sf) mice that are deficient in Tregs and succumb to severe multi-organ inflammation by 4 weeks of age...
May 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483914/tfe3-and-tfeb-transcriptionally-regulate-ppar%C3%AE-2-expression-in-adipocytes-and-mediate-adiponectin-and-glucose-levels-in-mice
#5
Nunciada Salma, Jun S Song, Akinori Kawakami, Suprabha P Devi, Mehdi Khaled, José M Cacicedo, David E Fisher
Members of the MiT transcription factor family are pivotal regulators of several lineage-selective differentiation programs. We show that two of these, Tfeb and Tfe3, control the regulator of adipogenesis, Pparγ2. Knockdown of Tfeb or Tfe3 expression during in vitro adipogenesis causes dramatic downregulation of Pparγ2 expression as well as adipogenesis. Additionally, we found that these factors regulate Pparγ2 in mature adipocytes. Next, we demonstrated that Tfeb and Tfe3 act directly by binding to consensus E-boxes within the Pparγ transcriptional regulatory region...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483913/antagonistic-interactions-between-erk-map-kinase-and-retinoic-acid-receptor-signaling-in-colorectal-cancer-cells
#6
Masamichi Imajo, Kunio Kondoh, Takuya Yamamoto, Kei Nakayama, May Nakajima-Koyama, Eisuke Nishida
Deregulated activation of RAS/ERK signaling and defects in retinoic acid receptor (RAR) signaling are both implicated in many types of cancers. However, interrelationships between these alterations in regulating cancer cell fates have not been fully elucidated. Here, we show that RAS/ERK and RAR signaling pathways antagonistically interact with each other to regulate colorectal cancer (CRC) cell fates. We show that RAR signaling activation promotes spontaneous differentiation of CRC cells, while ERK activation suppresses it...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483912/an-in-vitro-torc1-kinase-assay-that-recapitulates-the-gtr-independent-glutamine-responsive-torc1-activation-mechanism-on-yeast-vacuoles
#7
Mirai Tanigawa, Tatsuya Maeda
Evolutionarily-conserved TOR complex 1 (TORC1) responds to nutrients, especially amino acids, to promote cell growth. In yeast Saccharomyces cerevisiae, various nitrogen sources activate TORC1 with different efficiencies although the mechanism remains elusive. Leucine, and perhaps other amino acids, was reported to activate TORC1 via the heterodimeric small GTPases Gtr1-Gtr2, the orthologs of the mammalian Rag GTPases. More recently, an alternative Gtr-independent TORC1 activation mechanism that may respond to glutamine was reported, although its molecular detail is not clear...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483911/cd99-derived-agonist-ligands-inhibit-fibronectin-induced-activation-of-%C3%AE-1-integrin-through-pka-shp2-erk-ptpn12-fak-signaling-pathway
#8
Kyoung-Jin Lee, Yuri Kim, Yeon Ho Yoo, Min-Seo Kim, Sun-Hee Lee, Chang-Gyum Kim, Kyeonghan Park, Dooil Jeoung, Hansoo Lee, In Young Ko, Jang-Hee Hahn
The human CD99 protein is a 32kDa glycosylated transmembrane protein that regulates various cellular responses including cell adhesion and leukocyte extravasation. We previously reported that CD99 activation suppresses β1 integrin activity through dephosphorylation of FAK at Y397. We explored a molecular mechanism underlying the suppression of β1 integrin activity by CD99 agonists and its relevance to tumor growth in vivo CD99-Fc fusion proteins or a series of CD99-derived peptides suppressed β1 integrin activity by specifically interacting with three conserved motifs of the CD99 extracellular domain...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483910/rna-binding-by-the-histone-methyltransferases-set1-and-set2
#9
Camille Sayou, Gonzalo Millán-Zambrano, Helena Santos-Rosa, Elisabeth Petfalski, Samuel Robson, Jonathan Houseley, Tony Kouzarides, David Tollervey
Histone methylation at H3K4 and H3K36 is commonly associated with genes actively transcribed by RNA polymerase II (RNAPII) and is catalyzed by yeast Set1 and Set2, respectively. Here we report that both methyltransferases can be UV-crosslinked to RNA in vivo. High-throughput sequencing of the bound RNAs revealed strong Set1 enrichment near the transcription start site, whereas Set2 was distributed along pre-mRNAs. A subset of transcripts showed notably high enrichment for Set1 or Set2 binding relative to RNAPII, suggesting functional post-transcriptional interactions...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28483909/progerin-induced-replication-stress-facilitates-premature-senescence-in-hutchinson-gilford-progeria-syndrome
#10
Keith Wheaton, Denise Campuzano, Weili Ma, Michal Sheinis, Brandon Ho, Grant W Brown, Samuel Benchimol
Hutchinson-Gilford progeria syndrome (HGPS) is caused by a mutation in LMNA that produces an aberrant lamin A protein, progerin. The accumulation of progerin in HGPS cells leads to an aberrant nuclear morphology, genetic instability and p53-dependent premature senescence. How p53 is activated in response to progerin production is unknown. Here, we show that young, cycling HGPS fibroblasts, exhibit chronic DNA damage primarily in S phase as well as delayed replication fork progression. We demonstrate that progerin binds to PCNA altering its distribution away from replicating DNA in HGPS cells leading to γH2AX formation, ATR activation and RPA Ser33 phosphorylation...
May 8, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28461394/mrhl-lncrna-mediates-meiotic-commitment-of-mouse-spermatogonial-cells-by-regulating-sox8-expression
#11
Shubhangini Kataruka, Vijay S Akhade, Bhavana Kayyar, Manchanahalli R Satyanarayana Rao
Long non coding RNAs (lncRNAs) are important regulators of various biological processes including spermatogenesis. Our previous studies have shown the regulatory loop of mrhl RNA and Wnt signaling where mrhl RNA negatively regulates Wnt signaling and gets down regulated upon Wnt signaling activation. This down regulation of mrhl RNA is important for the meiotic progression of spermatogonial cells. In our present study, we identify the transcription factor Sox8 as the regulatory link between mrhl RNA expression, Wnt signaling activation and meiotic progression...
May 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28461393/crebh-maintains-circadian-glucose-homeostasis-by-regulating-hepatic-glycogenolysis-and-gluconeogenesis
#12
Hyunbae Kim, Ze Zheng, Paul D Walker, Gregory Kapatos, Kezhong Zhang
Cyclic AMP responsive element binding protein, hepatic specific (CREBH) is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate hepatic acute-phase response and lipid homeostasis. In this study, we demonstrated that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. CREBH proteolytic cleavage and post-translational acetylation modification are regulated under the circadian clock. Functionally, CREBH is required to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels...
May 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416638/eya2-a-target-activated-by-plzf-is-critical-for-plzf-rara-induced-leukemogenesis
#13
Ryoichi Ono, Masahiro Masuya, Satomi Ishii, Naoyuki Katayama, Tetsuya Nosaka
PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416637/a-kinase-independent-role-for-cdk19-in-p53-response
#14
K Audrey Audetat, Matthew D Galbraith, Aaron T Odell, Thomas Lee, Ahwan Pandey, Joaquin M Espinosa, Robin D Dowell, Dylan J Taatjes
The human Mediator complex regulates RNA Polymerase II transcription genome-wide. A general factor that regulates Mediator function is the four-subunit kinase module, which contains either CDK8 or CDK19. Whereas CDK8 is linked to specific signaling cascades and oncogenesis, the cellular roles of its paralog, CDK19, are poorly studied. We discovered that osteosarcoma cells (SJSA) are naturally depleted of CDK8 protein. Whereas stable CDK19 knockdown was tolerated in SJSA cells, proliferation was reduced. Notably, proliferation defects were rescued upon re-expression of wild-type or kinase-dead CDK19...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416636/p53-dynamically-directs-tfiid-assembly-on-target-gene-promoters
#15
R A Coleman, Z Qiao, S K Singh, C S Peng, M Cianfrocco, Z Zhang, A Piasecka, H Aldeborgh, G Basishvili, W L Liu
p53 is a central regulator that turns on vast gene networks to maintain cellular integrity upon various stimuli. p53 activates transcription initiation in part by aiding recruitment of TFIID to the promoter. However, the precise means by which p53 dynamically interacts with TFIID to facilitate assembly on target gene promoters remains elusive. To address this key question, we have undertaken an integrated approach involving single molecule fluorescence microscopy, single particle cryo-electron microscopy, and biochemistry...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416635/vprbp-dcaf1-regulates-the-degradation-and-non-proteolytic-activation-of-the-cell-cycle-transcription-factor-foxm1
#16
Xianxi Wang, Anthony Arceci, Kelly Bird, Christine A Mills, Rajarshi Choudhury, Jennifer L Kernan, Chunxiao Zhou, Victoria Bae-Jump, Albert Bowers, Michael J Emanuele
The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies and linked to chromosome instability. We characterize here a Cullin4-based E3 ubiquitin ligase and its substrate receptor VprBP/DCAF1 (CRL4(VprBP)) that we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression strongly activates a FoxM1 transcriptional reporter...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416634/a-molecular-mechanism-to-switch-the-aryl-hydrocarbon-receptor-from-a-transcription-factor-to-an-e3-ubiquitin-ligase
#17
Sandra Luecke-Johansson, Michael Gralla, Helene Rundqvist, Jolene Caifeng Ho, Randall S Johnson, Katarina Gradin, Lorenz Poellinger
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is known as a mediator of toxic responses. Recently, it was shown that AhR has dual functions. Besides being a transcription factor it also possesses an intrinsic E3 ubiquitin ligase function that targets e.g. the steroids receptors for proteasomal degradation. The aim of the study was to identify the molecular switch that determines whether AhR acts as a transcription factor or an E3 ubiquitin ligase. To do that, we used the breast cancer cell line MCF7, which expresses a functional ERα signaling pathway...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28396559/an-mrna-capping-enzyme-targets-fact-to-the-active-gene-to-enhance-the-engagement-of-rna-polymerase-ii-into-transcriptional-elongation
#18
Rwik Sen, Amala Kaja, Jannatul Ferdoush, Shweta Lahudkar, Priyanka Barman, Sukesh R Bhaumik
We have recently demonstrated that an mRNA-capping enzyme, Cet1, impairs promoter proximal accumulation/pausing of RNA polymerase II (pol-II) independently of its capping activity in Saccharomyces cerevisiae to control transcription. However, it is yet unknown how pol-II pausing is regulated by Cet1. Here, we show that Cet1's N-terminal domain (NTD) promotes the recruitment of FACT (FAcilitates Chromatin Transcription that enhances engagement of pol-II into transcriptional elongation) to the coding sequence of an active gene, ADH1, independently of mRNA-capping activity...
April 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28373292/caloric-restriction-extends-yeast-chronological-lifespan-by-optimizing-the-snf1-ampk-signaling-pathway
#19
Margaret B Wierman, Nazif Maqani, Erika Strickler, Mingguang Li, Jeffrey S Smith
AMP-activated protein kinase (AMPK) and the homologous yeast SNF1 complex, are key regulators of energy metabolism that counteract nutrient deficiency and ATP depletion by phosphorylating multiple enzymes and transcription factors that maintain energetic homeostasis. AMPK/SNF1 also promotes longevity in several model organisms, including yeast. Here we investigate the role of yeast SNF1 in mediating the extension of chronological lifespan (CLS) by caloric restriction (CR). We find that SNF1 activity is required throughout the log to stationary phase transition (diauxic shift) for effective CLS extension...
April 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28373291/dual-mechanism-of-rag-gene-repression-by-c-myb-during-pre-b-cell-proliferation
#20
Greg A Timblin, Liangqi Xie, Robert Tjian, Mark S Schlissel
Developing B lymphocytes undergo clonal expansion following successful immunoglobulin heavy chain gene rearrangement. During this proliferative burst, expression of the Rag genes is transiently repressed to prevent the generation of dsDNA breaks in cycling large pre-B cells. The Rag genes are then re-expressed in small resting pre-B cells for immunoglobulin light chain gene rearrangement. We previously identified c-Myb as a repressor of Rag transcription during clonal expansion using Abelson murine leukemia virus-transformed B cells...
April 3, 2017: Molecular and Cellular Biology
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